2019-05-25T17:59:57Zhttps://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/28892016-02-16T02:38:28Zcom_10261_25com_10261_1col_10261_278Rubio, DanielGarcía, SilviaPaz, María F.Cueva, Teresa de laLópez-Fernández, Luis A.Lloyd, Alison C.García-Castro, JavierBernad, Antonio2008-02-07T00:09:08Z2008-02-07T00:09:08Z2008-01-02PLoS ONE. 2008; 3(1): e1398.1932-6203http://hdl.handle.net/10261/288910.1371/journal.pone.0001398Background. We previously reported the in vitro spontaneous transformation of human mesenchymal stem cells (MSC) generating a population with tumorigenic potential, that we termed transformed mesenchymal cells (TMC).Methodology/Principal Findings. Here we have characterized the molecular changes associated with TMC generation. Using microarrays techniques we identified a set of altered pathways and a greater number of downregulated than upregulated genes during MSC transformation, in part due to the expression of many untranslated RNAs in MSC. Microarray results were validated by qRT-PCR and protein detection.Conclusions/Significance. In our model, the transformation process takes place through two sequential steps; first MSC bypass senescence by upregulating c-myc and repressing p16 levels. The cells then bypass cell crisis with acquisition of telomerase activity, Ink4a/Arf locus deletion and Rb hyperphosphorylation. Other transformation-associated changes include modulation of mitochondrial metabolism, DNA damage-repair proteins and cell cycle regulators. In this work we have characterized the molecular mechanisms implicated in TMC generation and we propose a two-stage model by which a human MSC becomes a tumor cell.engopenAccessMolecular Characterization of Spontaneous Mesenchymal Stem Cell TransformationArtículo